The objective is to evaluate the factors responsible for the decrease in energy expenditure accompanying hypocaloric dieting. We will focus on the role of dietary carbohydrate and protein intake in modifying the adaptation to caloric restriction. Preliminary studies have shown that the inclusion of sucrose in low calorie diets prevents the fall in metabolic rate produced by caloric restriction. We will examine the mechanisms underlying this effect by focusing on T3 and catecholamines and their interactions as well as the potential contribution of changes in protein turnover. The protocols are divided into two phases. Phase I will compare the adaptive responses of obese human subjects to low calorie diets that are either a) totally devoid of carbohydrate (80% fat, 20% protein), b) predominantly sucrose (80% sucrose, 20% protein), or c) pure sucrose. This will allow us to examine the influence of sucrose under conditions of constant protein intake and determine whether the apparent effect of sucrose may be due to accompanying protein deficiency. Phase II will be an in depth examination of the response to manipulation of T3 during low and high carbohydrate hypocaloric diets. The following questions will be addressed: 1) Is the fall in T3 seen during carbohydrate free hypocaloric feeding responsible for the decline in energy expenditure and other adaptations (eg protein metabolism) induced by such diets? (This will be examined by maintaining T3 with an exogenous supplement during carbohydrate free dieting.) 2) Does sucrose prevent the fall in metabolic rate induced by hypocaloric diet by maintaining circulating T3? (Iopanoic acid will be given during high carbohydrate low calorie dieting, to artificially lower T3 during this diet.) The mechanisms responsible for dietary thermic adaptations will be assessed by examining total and free T3, sympathetic nervous system activity, sensitivity to norepinephrine, nitrogen balance, and leucine turnover. Energy expenditure will be examined by periodic measurements of basal and resting metabolic rate, meal stimulated thermogenesis and the thermogenic response to norepinephrine infusion. In addition, our assessments of protein metabolism will be used to evaluate the role of T3 in the conservation of body protein stores during caloric restriction. The data will provide important new information regarding why obese people have difficulty in losing weight during dieting and may give insights about ways to overcome this important health problem.